Aicardi goutieres syndrome is associated with pulmonary hypertension
Aicardi goutieres syndrome is associated with pulmonary hypertension
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DOI：
10.1016/j.ymgme.2018.09.004
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发表时间：
2018-12-01
影响因子：
3.8
通讯作者：
Vanderver, Adeline L.
中科院分区：
文献类型：
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作者：
Adang, Laura A.;Frank, David B.;Vanderver, Adeline L.
虽然肺动脉高压（PH）是许多炎症性疾病的潜在威胁生命的并发症，但Aicardi Goutieres综合征（AGS）（一种罕见的干扰素（IFN）过量产生的遗传原因）与PH的发展之间的关联迄今尚未确定。我们采用回顾性图表分析了髓鞘疾病生物登记项目中AGS患者的心功能（n = 61）。尽可能获得其他前瞻性超声心动图（n = 22）。通过测量I型IFN诱导基因（干扰素信号基因或ISG）的mRNA转录物来计算IFN特征评分，这是全身性炎症的标志物。根据尸检样本进行病理分析。在我们的队列中，有4个人被确定受到PH的影响：3人在IFIH1基因中具有致病性功能获得性突变，1人具有杂合TREX1突变。所有被研究的AGS患者都注意到IFN特征评分升高(Mann-Whitney p
While pulmonary hypertension (PH) is a potentially life threatening complication of many inflammatory conditions, an association between Aicardi Goutieres syndrome (AGS), a rare genetic cause of interferon (IFN) overproduction, and the development of PH has not been characterized to date.We analyzed the cardiac function of individuals with AGS enrolled in the Myelin Disorders Bioregistry Project using retrospective chart review (n = 61). Additional prospective echocardiograms were obtained when possible (n = 22). An IFN signature score, a marker of systemic inflammation, was calculated through the measurement of mRNA transcripts of type I IFN-inducible genes (interferon signaling genes or ISG). Pathologic analysis was performed as available from autopsy samples. Within our cohort, four individuals were identified to be affected by PH: three with pathogenic gain-of-function mutations in the IFIH1 gene and one with heterozygous TREX1 mutations. All studied individuals with AGS were noted to have elevated IFN signature scores (Mann-Whitney p